Diagnostic performance of transthyretin measurement in fat tissue of patients with ATTR amyloidosis

In this article, the diagnostic performance of a transthyretin (TTR) ELISA for detection and characterization of transthyretin-derived (ATTR) amyloid in abdominal subcutaneous fat tissue was studied. Fat tissue specimens were analyzed of 38 patients with ATTR amyloidosis, 70 controls, and 17 carriers of a TTR mutation. Amyloid amount was graded semi-quantitatively in Congo red-stained specimens (0-4+). Amyloid was extracted from tissue in guanidine, and the TTR concentration was measured using a sandwich TTR-ELISA. The TTR concentration of patients with ATTR amyloidosis (mean 0.84 ng/mg fat tissue) was significantly higher than controls (p<0.001). With a TTR concentration of 0.13 ng/mg fat tissue as cut-off value, 32 of the 38 ATTR patients were identified resulting in a sensitivity of 84%. Sixty-seven of the 70 controls had values below the cut-off value resulting in a specificity of 96%. Thus, measuring TTR in fat tissue is useful for detecting ATTR amyloidosis and for characterizing amyloid as ATTR type

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

OBJECTIVE: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. METHODS: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. RESULTS: sNfL levels were increased both in 10 AL/PNP+ patients (p  I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. CONCLUSION: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis

Cardiac [^99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis:an early follow-up marker?

Purpose: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. Methods: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. Results: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p &lt;.001) in patients treated with patisiran for 29 [15–34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [3.39 to 5.80] (p =.010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p =.025). All other parameters did not change during treatment with a TTR-stabilizer. Conclusion: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.</p

Hillslope Hydrology in Global Change Research and Earth System Modeling

Earth System Models (ESMs) are essential tools for understanding and predicting global change, but they cannot explicitly resolve hillslope‐scale terrain structures that fundamentally organize water, energy, and biogeochemical stores and fluxes at subgrid scales. Here we bring together hydrologists, Critical Zone scientists, and ESM developers, to explore how hillslope structures may modulate ESM grid‐level water, energy, and biogeochemical fluxes. In contrast to the one‐dimensional (1‐D), 2‐ to 3‐mdeep, and free‐draining soil hydrology in most ESM land models, we hypothesize that 3‐D, lateral ridge‐to‐valley flow through shallow and deep paths and insolation contrasts between sunny and shady slopes are the top two globally quantifiable organizers of water and energy (and vegetation) within an ESM grid cell. We hypothesize that these two processes are likely to impact ESM predictions where (and when) water and/or energy are limiting. We further hypothesize that, if implemented in ESM land models, these processes will increase simulated continental water storage and residence time, buffering terrestrial ecosystems against seasonal and interannual droughts. We explore efficient ways to capture these mechanisms in ESMs and identify critical knowledge gaps preventing us from scaling up hillslope to global processes. One such gap is our extremely limited knowledge of the subsurface, where water is stored (supporting vegetation) and released to stream baseflow (supporting aquatic ecosystems). We conclude with a set of organizing hypotheses and a call for global syntheses activities and model experiments to assess the impact of hillslope hydrology on global change predictions

Hillslope Hydrology in Global Change Research and Earth System Modeling

Earth System Models (ESMs) are essential tools for understanding and predicting global change, but they cannot explicitly resolve hillslope-scale terrain structures that fundamentally organize water, energy, and biogeochemical stores and fluxes at subgrid scales. Here we bring together hydrologists, Critical Zone scientists, and ESM developers, to explore how hillslope structures may modulate ESM grid-level water, energy, and biogeochemical fluxes. In contrast to the one-dimensional (1-D), 2- to 3-m deep, and free-draining soil hydrology in most ESM land models, we hypothesize that 3-D, lateral ridge-to-valley flow through shallow and deep paths and insolation contrasts between sunny and shady slopes are the top two globally quantifiable organizers of water and energy (and vegetation) within an ESM grid cell. We hypothesize that these two processes are likely to impact ESM predictions where (and when) water and/or energy are limiting. We further hypothesize that, if implemented in ESM land models, these processes will increase simulated continental water storage and residence time, buffering terrestrial ecosystems against seasonal and interannual droughts. We explore efficient ways to capture these mechanisms in ESMs and identify critical knowledge gaps preventing us from scaling up hillslope to global processes. One such gap is our extremely limited knowledge of the subsurface, where water is stored (supporting vegetation) and released to stream baseflow (supporting aquatic ecosystems). We conclude with a set of organizing hypotheses and a call for global syntheses activities and model experiments to assess the impact of hillslope hydrology on global change predictions. Plain Language Summary Hillslopes are key landscape features that organize water availability on land. Valley bottoms are wetter than hilltops, and sun-facing slopes are warmer and drier than shaded ones. This hydrologic organization leads to systematic differences in soil and vegetation between valleys and hilltops, and between sunny and shady slopes. Although these patterns are fundamental to understanding the structures and functions of water and terrestrial ecosystems, they are too fine grained to be represented in global-scale Earth System Models. Here we bring together Critical Zone scientists who study the interplay of vegetation, the porous upper layer of the continental crust from vegetation to bedrock, and moisture dynamics deep into the weathered bedrock underlying hillslopes and Earth System Model scientists who develop global models, to ask: Do hillslope-scale processes matter to predicting global change? The answers will help scientists understand where and why hillslopes matter, and to better predict how terrestrial ecosystems, including societies, may affect and be affected by our rapidly changing planet.National Science Foundation [NSF-EAR-1528298, NSF-EAR-0753521]6 month embargo; published online: 27 February 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis

Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes.

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